Upregulate KIF4A Enhances Proliferation, Invasion of Hepatocellular Carcinoma and Indicates poor prognosis Across Human Cancer Types

Sci Rep. 2017 Jun 23;7(1):4148. doi: 10.1038/s41598-017-04176-9.

Abstract

Hepatocellular carcinoma (HCC) is one of the most aggressive and heterogeneous cancers worldwide. Herein, we demonstrate KIF4A (Chromosome-associated kinesin KIF4A) as a potential biomarker, is up-regulated in most samples of HCC. The expression level of KIF4A in tumor tissue is significantly associated with the survival time, and a significant correlation between KIF4A expression and clinical information stage, metastasis and tumor dimension was observed. We further measured the proliferation and migration ability of two HCC cell lines, HCC-LM3 and PLC/PRF/5, following KIF4A-siRNA transfection. Knocking down of KIF4A significantly reduced migration and proliferation ability. Moreover, we also measured the proliferation and migration ability of two HCC cell lines through KIF4A overexpression, and found that KIF4A overexpression could enhance migration and proliferation ability, indicating that KIF4A exhibits oncogenic effects. Besides, study based on TCGA cohorts also reveals high KIF4A mRNA expression are significantly associated with shorter overall survival in multiple cancer types. Gene sets enrichment analysis exhibited that cell cycle related pathways and p53 signaling pathways to be top altered pathways of in KIF4A-high expression group in HCC, suggesting the potential role of KIF4A in mediating tumor initiation and progression. In summary, our work identified KIF4A as a potential predictive and prognostic marker for hepatocellular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kinesins / genetics*
  • Kinesins / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Up-Regulation / genetics*

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • KIF4A protein, human
  • Kinesins